Elucidating the aetiology of human Campylobacter coli infections

Peer reviewedPublisher PD

Quantum phase transition in a single-molecule quantum dot

Quantum criticality is the intriguing possibility offered by the laws of quantum mechanics when the wave function of a many-particle physical system is forced to evolve continuously between two distinct, competing ground states. This phenomenon, often related to a zero-temperature magnetic phase transition, can be observed in several strongly correlated materials such as heavy fermion compounds or possibly high-temperature superconductors, and is believed to govern many of their fascinating, yet still unexplained properties. In contrast to these bulk materials with very complex electronic structure, artificial nanoscale devices could offer a new and simpler vista to the comprehension of quantum phase transitions. This long-sought possibility is demonstrated by our work in a fullerene molecular junction, where gate voltage induces a crossing of singlet and triplet spin states at zero magnetic field. Electronic tunneling from metallic contacts into the $\rm{C_{60}}$ quantum dot provides here the necessary many-body correlations to observe a true quantum critical behavior.Comment: 8 pages, 5 figure

Roadmap on multiscale materials modeling

Modeling and simulation is transforming modern materials science, becoming an important tool for the discovery of new materials and material phenomena, for gaining insight into the processes that govern materials behavior, and, increasingly, for quantitative predictions that can be used as part of a design tool in full partnership with experimental synthesis and characterization. Modeling and simulation is the essential bridge from good science to good engineering, spanning from fundamental understanding of materials behavior to deliberate design of new materials technologies leveraging new properties and processes. This Roadmap presents a broad overview of the extensive impact computational modeling has had in materials science in the past few decades, and offers focused perspectives on where the path forward lies as this rapidly expanding field evolves to meet the challenges of the next few decades. The Roadmap offers perspectives on advances within disciplines as diverse as phase field methods to model mesoscale behavior and molecular dynamics methods to deduce the fundamental atomic-scale dynamical processes governing materials response, to the challenges involved in the interdisciplinary research that tackles complex materials problems where the governing phenomena span different scales of materials behavior requiring multiscale approaches. The shift from understanding fundamental materials behavior to development of quantitative approaches to explain and predict experimental observations requires advances in the methods and practice in simulations for reproducibility and reliability, and interacting with a computational ecosystem that integrates new theory development, innovative applications, and an increasingly integrated software and computational infrastructure that takes advantage of the increasingly powerful computational methods and computing hardware

Using sequence data to identify alternative routes and risk of infection: a case-study of campylobacter in Scotland

<b>Background:</b> Genetic typing data are a potentially powerful resource for determining how infection is acquired. In this paper MLST typing was used to distinguish the routes and risks of infection of humans with Campylobacter jejuni from poultry and ruminant sources.<p></p> <b>Methods:</b> C. jejuni samples from animal and environmental sources and from reported human cases confirmed between June 2005 and September 2006 were typed using MLST. The STRUCTURE software was used to assign the specific sequence types of the sporadic human cases to a particular source. We then used mixed case-case logistic regression analysis to compare the risk factors for being infected with C. jejuni from different sources.<p></p> <b>Results:</b> A total of 1,599 (46.3%) cases were assigned to poultry, 1,070 (31.0%) to ruminant and 67 (1.9%) to wild bird sources; the remaining 715 (20.7%) did not have a source that could be assigned with a probability of greater than 0.95. Compared to ruminant sources, cases attributed to poultry sources were typically among adults (odds ratio (OR) = 1.497, 95% confidence intervals (CIs) = 1.211, 1.852), not among males (OR = 0.834, 95% CIs = 0.712, 0.977), in areas with population density of greater than 500 people/km(2) (OR = 1.213, 95% CIs = 1.030, 1.431), reported in the winter (OR = 1.272, 95% CIs = 1.067, 1.517) and had undertaken recent overseas travel (OR = 1.618, 95% CIs = 1.056, 2.481). The poultry assigned strains had a similar epidemiology to the unassigned strains, with the exception of a significantly higher likelihood of reporting overseas travel in unassigned strains.<p></p> <b>Conclusions:</b> Rather than estimate relative risks for acquiring infection, our analyses show that individuals acquire C. jejuni infection from different sources have different associated risk factors. By enhancing our ability to identify at-risk groups and the times at which these groups are likely to be at risk, this work allows public health messages to be targeted more effectively. The rapidly increasing capacity to conduct genetic typing of pathogens makes such traced epidemiological analysis more accessible and has the potential to substantially enhance epidemiological risk factor studies

Maternal smoking during pregnancy increases the risk of recurrent wheezing during the first years of life (BAMSE)

BACKGROUND: Exposure to cigarette smoking during foetal and early postnatal life may have implications for lung health. The aim of this study was to assess the possible effects of such exposure in utero on lower respiratory disease in children up to two years of age. METHODS: A birth cohort of 4089 newborn infants was followed for two years using parental questionnaires. When the infant was two months old the parents completed a questionnaire on various lifestyle factors, including maternal smoking during pregnancy and after birth. At one and two years of age information was obtained by questionnaire on symptoms of allergic and respiratory diseases as well as on environmental exposures, particularly exposure to environmental tobacco smoke (ETS). Adjustments were made for potential confounders. RESULTS: When the mother had smoked during pregnancy but not after that, there was an increased risk of recurrent wheezing up to two years' age, OR(adj )= 2.2, (95% CI 1.3 – 3.6). The corresponding OR was 1.6, (95% CI 1.2 – 2.3) for reported exposure to ETS with or without maternal smoking in utero. Maternal smoking during pregnancy but no exposure to ETS also increased the risk of doctor's diagnosed asthma up to two years of age, OR(adj )= 2.1, (95% CI 1.2 – 3.7). CONCLUSION: Exposure to maternal cigarette smoking in utero is a risk factor for recurrent wheezing, as well as doctor's diagnosed asthma in children up to two yearsof age

Geographic determinants of reported human Campylobacter infections in Scotland

<p><b>Background:</b> Campylobacteriosis is the leading cause of bacterial gastroenteritis in most developed countries. People are exposed to infection from contaminated food and environmental sources. However, the translation of these exposures into infection in the human population remains incompletely understood. This relationship is further complicated by differences in the presentation of cases, their investigation, identification, and reporting; thus, the actual differences in risk must be considered alongside the artefactual differences.</p> <p><b>Methods:</b> Data on 33,967 confirmed Campylobacter infections in mainland Scotland between 2000 and 2006 (inclusive) that were spatially referenced to the postcode sector level were analysed. Risk factors including the Carstairs index of social deprivation, the easting and northing of the centroid of the postcode sector, measures of livestock density by species and population density were tested in univariate screening using a non-spatial generalised linear model. The NHS Health Board of the case was included as a random effect in this final model. Subsequently, a spatial generalised linear mixed model (GLMM) was constructed and age-stratified sensitivity analysis was conducted on this model.</p> <p><b>Results:</b> The spatial GLMM included the protective effects of the Carstairs index (relative risk (RR) = 0.965, 95% Confidence intervals (CIs) = 0.959, 0.971) and population density (RR = 0.945, 95% CIs = 0.916, 0.974. Following stratification by age group, population density had a significant protective effect (RR = 0.745, 95% CIs = 0.700, 0.792) for those under 15 but not for those aged 15 and older (RR = 0.982, 95% CIs = 0.951, 1.014). Once these predictors have been taken into account three NHS Health Boards remain at significantly greater risk (Grampian, Highland and Tayside) and two at significantly lower risk (Argyll and Ayrshire and Arran).</p> <p><b>Conclusions:</b> The less deprived and children living in rural areas are at the greatest risk of being reported as a case of Campylobacter infection. However, this analysis cannot differentiate between actual risk and heterogeneities in individual reporting behaviour; nevertheless this paper has demonstrated that it is possible to explain the pattern of reported Campylobacter infections using both social and environmental predictors.</p&gt

LDL-cholesterol concentrations: a genome-wide association study

BACKGROUND: LDL cholesterol has a causal role in the development of cardiovascular disease. Improved understanding of the biological mechanisms that underlie the metabolism and regulation of LDL cholesterol might help to identify novel therapeutic targets. We therefore did a genome-wide association study of LDL-cholesterol concentrations. METHODS: We used genome-wide association data from up to 11,685 participants with measures of circulating LDL-cholesterol concentrations across five studies, including data for 293 461 autosomal single nucleotide polymorphisms (SNPs) with a minor allele frequency of 5% or more that passed our quality control criteria. We also used data from a second genome-wide array in up to 4337 participants from three of these five studies, with data for 290,140 SNPs. We did replication studies in two independent populations consisting of up to 4979 participants. Statistical approaches, including meta-analysis and linkage disequilibrium plots, were used to refine association signals; we analysed pooled data from all seven populations to determine the effect of each SNP on variations in circulating LDL-cholesterol concentrations. FINDINGS: In our initial scan, we found two SNPs (rs599839 [p=1.7x10(-15)] and rs4970834 [p=3.0x10(-11)]) that showed genome-wide statistical association with LDL cholesterol at chromosomal locus 1p13.3. The second genome screen found a third statistically associated SNP at the same locus (rs646776 [p=4.3x10(-9)]). Meta-analysis of data from all studies showed an association of SNPs rs599839 (combined p=1.2x10(-33)) and rs646776 (p=4.8x10(-20)) with LDL-cholesterol concentrations. SNPs rs599839 and rs646776 both explained around 1% of the variation in circulating LDL-cholesterol concentrations and were associated with about 15% of an SD change in LDL cholesterol per allele, assuming an SD of 1 mmol/L. INTERPRETATION: We found evidence for a novel locus for LDL cholesterol on chromosome 1p13.3. These results potentially provide insight into the biological mechanisms that underlie the regulation of LDL cholesterol and might help in the discovery of novel therapeutic targets for cardiovascular disease

Do parents who smoke underutilize health care services for their children? A cross sectional study within the longitudinal PIAMA study

Background. A higher prevalence of respiratory symptoms and an associated increase in health care utilization among children with parents who smoke is to be expected. From previous studies however, it appears that parents who smoke may underutilize health services for their children, especially with respect to respiratory care. This study explores the validity and generalizability of the previous assumption. Methods. Data were obtained from a Dutch birth-cohort study; the Prevention and Incidence of Asthma and Mite Allergy (PIAMA) project. Information regarding parental smoking, the child's respiratory symptoms and health care use and potential confounders were obtained by postal questionnaires. Multivariate logistic models were used to relate parental smoking to the child's respiratory symptoms and health care use. Results. The study comprised 3,564, 4-year old children. In the crude analysis, respiratory symptoms were more frequent among children with a parent who smoked, while health care utilization for respiratory symptoms was not significantly different between children with or without a parent who smoked. In the multivariate analyses, maternal smoking had a larger impact on the child's respiratory symptoms and health care use as compared to paternal smoking. Maternal smoking was positively associated with mild respiratory symptoms of the child, adjusted odds ratio [AOR] 1.50 (1.19-1.91), but not with severe respiratory symptoms AOR 1.03 (0.75-1.40). Among children with mild respiratory symptoms, children with a mother who smoked were less likely to be taken to the general practitioner (GP) for respiratory symptoms, than children with mothers who did not smoke, AOR 0.58 (0.33-1.01). This finding was less pronounced among children with severe respiratory symptoms AOR 0.86 (0.49-1.52). Neither GP visits for non-respiratory symptoms nor specialized care for respiratory disease were significantly associated with parental smoking. Conclusion. Mothers who smoke appear to underutilize health care for their children with mild respiratory symptoms. Health care workers should be informed about this phenomenon. Inquiring after the respiratory health of the children during regular visits to healthy baby clinics may help to tr

Hundreds of variants clustered in genomic loci and biological pathways affect human height

Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P < 0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.

Overweight/Obesity and Respiratory and Allergic Disease in Children: International Study of Asthma and Allergies in Childhood (ISAAC) Phase Two

BackgroundChildhood obesity and asthma are increasing worldwide. A possible link between the two conditions has been postulated.MethodsCross-sectional studies of stratified random samples of 8–12-year-old children (n = 10 652) (16 centres in affluent and 8 centres in non-affluent countries) used the standardized methodology of ISAAC Phase Two. Respiratory and allergic symptoms were ascertained by parental questionnaires. Tests for allergic disease were performed. Height and weight were measured, and overweight and obesity were defined according to international definitions. Prevalence rates and prevalence odds ratios were calculated.ResultsOverweight (odds ratio = 1.14, 95%-confidence interval: 0.98; 1.33) and obesity (odds ratio = 1.67, 95%-confidence interval: 1.25; 2.21) were related to wheeze. The relationship was stronger in affluent than in non-affluent centres. Similar results were found for cough and phlegm, rhinitis and eczema but the associations were mostly driven by children with wheeze. There was a clear association of overweight and obesity with airways obstruction (change in FEV1/FVC, −0.90, 95%-confidence interval: −1.33%; −0.47%, for overweight and −2.46%, 95%-confidence interval: −3.84%; −1.07%, for obesity) whereas the results for the other objective markers, including atopy, were null.ConclusionsOur data from a large international child population confirm that there is a strong relation of body mass index with wheeze especially in affluent countries. Moreover, body mass index is associated with an objective marker of airways obstruction (FEV1/FVC) but no other objective markers of respiratory and allergic disorders